The sesquiterpene cyclases are a class of enzymes that covert a common substrate, farnesyl disphosphate, to over 300 different cyclization products. Trichodiene synthase from Fusarium sporotrichoides is a sesquiterpene cyclase that catalyzes the formation of trichodiene in the first committed step in the biosynthesis of trichothecane mycotoxins and antibiotics. While the enzymology and mechanism of this enzyme have been thoroughly studied, atomic structural data are needed to fully understand the mechanism. Structural studies of trichodiene synthase will elucidate the steric and electronic features of the active site that control the course of the reaction. Comparison of this structure to other sesquiterpene cyclase structures will also demonstrate the mechanisms this class of enzymes uses to dictate the stereochemical and regiochemical outcomes of these complex reactions that lead to use a diversity of products.